A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

STUDY DESIGN: Experimental study. OBJECTIVES: The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). SETTING: The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. METHODS: A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. RESULTS: Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). CONCLUSIONS: We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Need for validation of clinical decision aids: use of the AST/ALT ratio in predicting cirrhosis in chronic hepatitis C.

OBJECTIVE: A value of > or = 1 for the ratio of aspartate amino-transferase to alanine aminotransferase (the AST/ALT ratio or AAR) has been shown to have a positive predictive value of 100% for the diagnosis of cirrhosis in patients with chronic hepatitis C. If validated on separate cohorts, an AAR > or = 1 might obviate the need for liver biopsy in some patients with hepatitis C. METHODS: We attempted to validate the AAR by abstracting demographic and clinical data from a database of consecutive patients with hepatitis C who had a liver biopsy between 1993 and 1998. We used definitions, methods of data collection, and analyses comparable to those of the published study. A hepatopathologist blindly reviewed 49 liver biopsies for histological grade and stage. RESULTS: The current cohort of 177 patients and the previous cohort of 139 patients were comparable in mean age (42.3 vs 43.8 yr), percentage of men (63 vs 67), percentage with an AAR > or =1 (20 vs 17), and Child-Pugh distribution, but differed in substantial use of ethanol (11% vs 3.6%; p = 0.01) and in the prevalence of cirrhosis (23% vs 34%, p = 0.06). Respective sensitivities of the AAR were 56% and 53%. An AAR > or =1 had a positive predictive value of 64% (95% confidence interval 48-78%) for the current cohort. Thirteen of 36 patients (36%) with an AAR > or =1 were incorrectly identified as having cirrhosis. Of these 13 patients, 6 had a normal AST and ALT, 5 had a minimally elevated AST or ALT, and 1 had advanced fibrosis without cirrhosis. CONCLUSIONS: These results suggest that an AAR > or =1 may not be as useful for predicting cirrhosis in chronic hepatitis C as previously thought, and emphasizes the need for validation of clinical decision aids on independent patient cohorts.

5-year incidence of adenomas after negative colonoscopy in asymptomatic average-risk persons [see comment].

BACKGROUND & AIMS: Cost-effectiveness of colorectal cancer screening will be maximized by selecting the widest screening intervals that effectively prevent cancer mortality. However, data on the incidence of neoplasia in persons with no abnormal findings on initial examination are limited. The aim of this study was to describe the incidence of colonic neoplasia 5 years after negative screening colonoscopy in asymptomatic average-risk persons. METHODS: We previously reported the results of screening colonoscopy in 496 asymptomatic average-risk persons, 368 of whom had no neoplasia identified. Colonoscopy to the cecum was performed in 154 of these persons at a mean of 66 months after the initial negative colonoscopy. RESULTS: Forty-one (27%) had at least one adenoma, but only 1 person had an adenoma > or = 1 cm and none had cancer, severe dysplasia, or villous or tubulovillous histology. Hyperplastic polyps at the initial examination did not predict incident adenomas. Regular nonsteroidal anti-inflammatory drug use was associated with a decreased rate of incident adenomas. CONCLUSIONS: In average-risk persons, the interval between screening examinations can be safely expanded beyond 5 years, provided the initial examination is a carefully performed complete colonoscopy that is negative for colonic adenomas or cancer.

Effects of ethanol administration on components of the ubiquitin proteolytic pathway in rat liver.

Hepatic protein accumulation during ethanol administration may result partly from an ethanol-elicited decline in hepatic protein degradation, which we have previously shown. We conducted the current studies to examine the effects of ethanol administration on the levels of hepatic ubiquitin, an 8.5-kd protein which is an important mediator of extralysosomal protein catabolism. Rats were pair-fed liquid diets containing either ethanol (36% of calories) or isocaloric maltose-dextrin for 1 to 5 weeks. Ubiquitin was immunochemically quantified by competitive enzyme-linked immunosorbent assay (ELISA) in crude cytosol fractions from whole liver and in 12,000g supernatants of hepatocyte lysates. Ubiquitin levels in hepatic cytosol fractions of ethanol-fed rats exceeded those of controls by about 30%. Isolated hepatocytes from ethanol-fed animals also showed a 40% to 75% elevation of ubiquitin above that in cells of pair-fed controls and this difference exceeded the relative rise in hepatocellular protein. In hepatocyte lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting, we detected monomeric ubiquitin and higher molecular mass ubiquitin-protein conjugates. However, the immunoblot analyses revealed no quantitative changes in the level of either free or conjugated ubiquitin. The ubiquitin conjugating activity of crude and diethyl aminoethyl-fractionated liver cytosols of ethanol-fed rats had equal capacities to those from controls in catalyzing the formation of ubiquitin-protein conjugates. Our findings indicate that chronic ethanol consumption increased the level of immunoreactive ubiquitin in rat liver. This may have resulted from enhanced ubiquitin production because of an ethanol-elicited stress response and/or decreased catabolism of ubiquitin and its conjugates. Our findings also provide no indication that the ethanol-elicited reduction in hepatic proteolysis is because of a ubiquitin-mediated mechanisms.

Cricopharyngeal dysfunction in Parkinson's disease: role in dysphagia and response to myotomy.

We report five patients with Parkinson's disease and dysphagia who were found, by radiological and manometric evaluation, to have evidence of cricopharyngeal dysfunction, which included the presence of a Zenker's diverticulum in two. Cricopharyngeal myotomy was performed in four patients with excellent and sustained improvement in swallowing. We conclude that cricopharyngeal function should be carefully evaluated in patients with Parkinson's disease and dysphagia and that surgical treatment should be considered in appropriate cases.